Natural product-based synthesis of novel anti-infective isothiocyanate- and isoselenocyanate-functionalized amphilectane diterpenes

The marine natural product (−)-8,15-diisocyano-11(20)-amphilectene (1), isolated from the Caribbean sponge Svenzea flava, was used as scaffold to synthetize five new products, all of which were tested against laboratory strains of Plasmodium falciparum and Mycobacterium tuberculosis H(37)Rv. The scaffold contains two isocyanide units that are amenable to chemical manipulation, enabling them to be elaborated into a small library of sulfur and selenium compounds. Although most of the analogs prepared were less potent than the parent compound, 5 was nearly equipotent showing IC(50) values of 0.0066 µM and 0.0025 µM, respectively, against two strains (Dd2 and 3D7) of the malaria parasite. On the other hand, when assayed against the tuberculosis bacterium, analogs 5 and 6 were found to be more potent than 1